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Hematology Block 3 > Chemotherapy > Flashcards

Chemotherapy Flashcards

(62 cards)

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1
Q

What classes fall under the category of traditional chemo?

A

Alkylating agents

antimetabolites

mitotic inhibitors

Topoisomerase inhibitors

Other “typical” chemotherapeutics

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2
Q

Examples of cell cycle nonspecific agents

A

Alkylating agents

Anthracyclines

Nitrosoureas

Platinum agents

I can take a NAAP at any time of day.

(Effects exerted at any phase of the cell cycle; toxic effects occur during cell cycle and are expressed during attempt at cell division)

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3
Q

Examples of Cell Cycle Specific agents:

A

Antimetabolites

Vincas

Taxanes

(Effect exerted on dividing cells only; not active in resting phase. Administrated as continuous infusion of multiple divided doses)

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4
Q

How are cell cycle specific chemo drugs administered?

A

As continuous infusion or multiple divided doses

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5
Q

What is the mechanism of action of alkylating agents?

A

Work via direct crosslinking of base pairs - prevent separation the strands and thus prevent cell division/proliferation

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6
Q

List typical alkylating agents used:

A

Cyclophosphamide (widely used)

Isofamide (used for sarcomas)

Melphalan (bone marrow, stem cell transplant)

Busulfan (bone marrow, stem cell transplant)

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7
Q

Typical alkylator toxicities (associated with alkylating agents):

A
  • Myelosuppression
  • Nausea/vomiting
  • Secondary malignancies
  • Infertility/impaired fertility
  • Hemorrhagic cystitis
    • Ifosfamide (and cyclophosphamide) produce acrolein metabolite, which binds to bladder wall and causes direct irritation, hematuria.
    • Use Mensa - this is a chemoprotectant - binds to acrolein, prevents it from binding to bladder wall and allows it to be excreted in urine. Use this along with Ifosfamide and high doses of cyclo.
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8
Q

What platinum compounds are used as atypical alkylators used in treatment?

A

Cisplatin

Carboplatin

Oxaliplatin

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9
Q

What toxicities are associated with Platinum compound (alkylating agents) treatment:

A

Peripheral neuropathies (e.g. like foot falls asleep)

  • Oxaliplatin: cold sensitivitiy (neuropathy esp. when skin exposed to cold)

Nephrotoxic (cisplatin) - need to make sure no prior renal disease

  • Prevention with forced diuresis, mannitol
  • Increased creatinine (3-6 days after administration)
  • Magnesium wasting - can go into renal failure

Nausea/vomiting (cisplatin)

Thrombocytopenia (carboplatin)

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10
Q

Have to be especially cautious of patient developing ____ as a result of Cisplatin administration.

A

Renal failure

This medication is extremely nephrotoxic

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11
Q

A patient receiving treatment with Cisplatin WILL experience ____ if not given medication

A

nausea/vomiting

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12
Q

Why must dosing be so careful with Carboplatin?

A

There is a dose-limiting toxicity that will cause platelets to plummet.

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13
Q

Examples of Nitrosureas:

A

BCNu (Carmustine)

CCNu (Lomustine)

(first developed for WWII mustard gas)

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14
Q

What toxities are associated with Nitrosureas? Why?

A

Pulmonary (BCNu)

Myelosuppression

Nausea/vomiting

Phlebitis

CNS (BCNU w/ ETOH dilution) - results from ETOH and not drug itself. Basically inebriated after treatment.

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15
Q

Antimetabolites are structurally similar to compounds needed for _____. They ultimately inhibit ____, and specifically target the __ phase.

A

Antimetabolites are structurally similar to compounds needed for normal cell function. They ultimately inhibit DNA replication or repair, and specifically target the S phase.

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16
Q

What are the 4 broad categories of Antimetabolites?

A

Folate antagonists

  • methotrexate
  • pemetrexed

Pyrimidine analogues

  • Fluorouracil
  • Capecitabine

Pyrimidine antagonists

  • Cytarabine

Purine antagonists

  • 6-mercaptopurine
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17
Q

Explain the dosing of methotrexate:

A

Large dose range

Higher doses (<100mg/m) require rescue with leucovorin and urine alkalinization (metabolites can crystallize in urine and damage tubules - can prevent this with alkalinization)

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18
Q

Toxicities associated with Methotrexate:

A

mucositis (painful sores in mouth)

myelosuppression

(usually see both symptoms in conjunction)

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19
Q

Pemetrexad is typically supplemented with WHAT?

A

Supplemented with folate and b12 - this is a folate antagonist drug, and supplementation with this helps prevent myelosuppression.

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20
Q

Does “rescue” folate supplementation impact tumor cells?

A

No!

Tumor cells rely solely on endogenous folate for growth

Normal cells can use exogenous folate to be rescued.

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21
Q

How is Fluorouracil administered?

A

Bolus or continuous infusion

(has impacts on types of side effects)

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22
Q

Continuous infusion of 5FU results in what toxicities?

Bolus administration of 5FU results in what toxicities?

A

Continuous - GI (mucositis, diarrhea)

Bolus - myelosuppression

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23
Q

5FU is commonly used in combination with _____. Why?

A

Commonly used with leucovorin - used to POTENTIATE the effects (enhance)

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24
Q

What is Capecitabine?

A

An oral fluorouracil prodrug

Known side effect is hand-foot syndrome (redness in hands and feet. Can progress to severe sloughing if treatment is continued)

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25
How does leucovorin potentiate fluorouracil?
Increases 5FU's binding affinity to thymidylate synthase. Strengthened affinity leads to greater inhibiton of dUMP-dTMP, potentiating 5FU's mechanism
26
Cytarabine is a ____ antagonist
pyrimidine
27
How is Cytarabine administered?
Continuous infusion and high dose (HIDAC)
28
Toxicities associated with high dose cytarabine (HIDAC)?
Cerebellar toxicity (increased incidence with renal dysfunction, Cr\>2) Conjunctivitis (eyedrops Q6 until 48 hours after last dose
29
List 4 purine antagonists (antimetabolites):
**6-mercaptopurine** Gemcitabine Cladribine (2-CDA) Fludarabine
30
What category of drug do Vinca Alkaloids fall under? Name 3 examples of the drugs
These are microtubule targeting agents Vincristine Vinblastine Vinorelbine
31
Vinca alkaloids are specific for the ___ phase of the cell cycle. Specifically, they target \_\_\_\_.
Vinca alkaloids are specific for the **M** phase of the cell cycle. Specifically, they target **microtubules (for destruction)**.
32
Toxicity of Vinca alkaloids:
Cumulative neurotoxicities Variable myelosuppression (vinBLASTine \> vincristine)
33
Vinca alkaloids can be fatal - how?
Fatal if administered intrathecally!!!
34
Taxanes are a category of drugs that target WHAT?
The **M phase** of cell cycle Cause **microtubule stabilization**
35
What are two examples of Taxanes?
Paclitaxel (Taxol) Docetaxel (Taxotere) These target the M phase, causing microtubular stabilization
36
Toxiticies associated with taxanes:
Myelosuppression Peripheral neuropathies Hypersensitivity (Cremaphor dilutent in paclitaxel \> Tween80 in docetaxel) - another example of mixture causing toxicity, not the drug itself
37
Topoisomerase I function:
Enzyme responsible for relaxing supercoiled DNA, to allow transcription to occur
38
Topoisomerase II function:
Enzyme responsible for recoiling DNA after transcription has occurred
39
What drugs target topoisomerase I?
Camptothecins * Topotecan * Irinotecan (more commonly used)
40
Toxicities associated with Camptothecin use:
Myelosuppression **Diarrhea (Irinotecan)** - "I ran to the can" - can result in severe electrolyte abnormalities and cardiac function * Early onset, self limiting - treat with atropine * Later onset, life-threatening - treat aggressively with **loperamide** (NO MAX DAILY DOSE)
41
Examples of Topoisomerase II inhibitors:
**Etoposide** (formulated in vehicle that causes hypotension in high doses) Teniposide
42
Toxicities associated with Etoposides:
Myelosuppression Secondary malignancies (AML with 11q23) Dose dependent mucositis (more with high dose)
43
Mechanism of Anthracyclines:
Intercalate DNA and inhibit topoisomerase Secondary mechanisms include free radical damage and perhaps some alkylation (originally developed as antibiotic)
44
Important examples of Anthracyclines include:
Doxorubicin (most solid tumors) Daunorubicin, idarubicin (acuke leukemias) Epirubicin (breast cancer) Mitoxantrone
45
Toxicities associated with Anthracyclines:
Myelosuppression **Cardiac toxicity**!!!! All cause cumulative, dose-dependent biventricular heart failure Mucositis **Extravasation** (super awful blistering and necrosis if improperly injected into tissue rather than vein)
46
Bleomycin is highly associated with ___ toxicity. Why?
**PULMONARY** toxicity (Interstitial pneumonitis, pulmonary fibrosis, and hypersensitivity pneumonitis) * Low hydrolase enzymes in lung (hydrolases inactivate bleomycin) * Endothelial cell injury --\> cytokine release * Oxygen free radicals; lipid peroxidation of membrane phospholipids * Interstitial edema * Stimulation of lung fibroblasts --\> collagen
47
Anti-estrogens (hormonal therapy for breast cancer) - examples:
Anti-estrogens: * Tamoxifen * Fulvestrant * Megestrol acetate (used as chemo and appetite stimulant at different doses) Aromatase inhibitors: * Anatrazole * Letrozole * Exemestane (irreversible)
48
Hormonal therapy (for prostate cancer) - examples:
Antiandrogens * Flutamide * Bicalutamide * Nilutamide LHRH agonists (tumor “flare”) * Leuprolide * Goserelin GnRH antagonist * Degarelix CYP17 Inhibitors * Abiraterone (androgen biosynthesis inhibitor)
49
Murine monoclonal antibodies:
100% **mouse** protein e.g. murom**onab**
50
Chimeric monoclonal antibodies:
Ch**im**eric - 33% mouse protein Cetux**imab** Ritux**imab**
51
Humanized monoclonal antibody:
Humanized - 10% mouse protein Bevaciz**umab** Trastuz**umab**
52
Human monoclonal antibody:
0% mouse protein e.g. panitu**mumab** **(never see hypersensitivity)**
53
Rituximab is a mab targeting \_\_\_\_, used to treat \_\_\_\_\_
Rituximab is a mab targeting **CD20**, used to treat **lymphoma**
54
Trastuzumab is a mab targeting \_\_\_\_\_, used to treat \_\_\_\_\_
Trastuzumab is a mab targeting **Her-2**, used to treat **Breast cancer**
55
Cetuximab is a mab targeting \_\_\_\_, used to treat \_\_\_\_\_
Cetuximab is a mab targeting **EGFR**, used to treat **solid tumors**
56
Bevacizumab is a mab targeting \_\_\_\_, used to treat \_\_\_\_\_
Bevacizumab is a mab targeting **VEGF**, used to treat **solid tumors**
57
Toxicity associated with Bevacizumab:
Proteinuria GI perforation
58
Toxicity associated with Cetuximab:
Severe hypersensitivity reactions Acneiform rash (actually correlates with higher survival)
59
"Targeted therapy" refers to WHAT
newer generation of agents targeted at cellular processes e.g. tyrosine kinase inhibitors like Imatinib (Gleevec)
60
Acneiform rash can be associated with tyrosine kinase therapies, especially those associated with ____ targets.
EGFR
61
Ipilimumab:
**Anti CTLA-4** CTLA-4 are like the brakes of the immune system. Tells the immune system to calm down. Tumor cells can ramp up CTLA-4 to turn off the immune system so they aren't recognized as foreign. These drugs block CTLA-4 so the immune system can function again.
62
Toxicities associated with Ipilimumab:
Toxicities are treated differently than standard toxicities. Treat many with **steroids**. Compared to e.g. severe diarrhea in patient being treated irinotecan who can be treated with just an anti-diarrheal. Here it's an autoimmune reaction, so these won't work.

Hematology Block 3 (8 decks)

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